Human amniotic mesenchymal stem cells alleviate lung injury induced by ischemia and reperfusion after cardiopulmonary bypass in dogs.

ABSTRACT

Transplantation of mesenchymal stem cells may inhibit pathological immune processes contributing to ischemia/reperfusion (I/R) injury. This study aimed to assess the capacity of human amniotic MSC (hAMSCs) to ameliorate I/R injury in a dog model of cardiopulmonary bypass (CPB). Dissociated hAMSCs were cultured ex vivo, and their immunophenotypes were assessed by flow cytometry and immunohistochemistry. A dog model of CPB was established by surgical blockage of the aorta for 1 h. Dogs either underwent mock surgery (Sham group), CPB (model group), or CPB, followed by femoral injection of 2 × 10(7) hAMSCs (n=6). Anti-human nuclei staining revealed hAMSCs in the lungs 3 h after surgery. Oxygen index (OI) and respiratory index (RI) of arterial blood were measured using a biochemical analyzer. Venous blood TNF-α, IL-8, MMP-9, and IL-10 concentrations were measured by ELISA. Pathological changes in the lung were assessed by light microscopy. Third-generation-cultured hAMSCs expressed high levels of CD29, CD44, CD49D, CD73, and CD166 levels, but low CD34 or CD45 amounts and their cytoplasm contained Vimentin. In CPB model animals, OI was elevated and RI reduced; TNF-α, IL-8, and MMP-9 levels were elevated, and IL-10 levels reduced within 3h (P<0.05), but hAMSC transplantation significantly ameliorated these changes (P<0.05). Pathological changes observed in the hAMSC group were significantly less severe than those in the CPB group. In conclusion, hAMSC transplantation can downregulate proinflammatory factors and reduce MMP-9 levels, whereas upregulating the anti-inflammatory molecule IL-10, thus reducing I/R lung injury in a dog model of CPB.